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Microbes inhabiting the human gastrointestinal tract have been under the spotlight during the last decade, given the multiple associations detected between specific microbiota profiles and health status. Diet is widely recognized as the primary environmental variable shaping the intestinal microbiota in humans. Therefore, the study of diet-microbiota-host interactions deserves special attention to provide clues to several diseases, including cognitive, metabolic, and immune ones. In a similar manner, the investigation of the molecular cross-talk between host cells and microbes in a particular nutritional environment also serves as the foundation for design of innovative therapeutic strategies based on probiotics, prebiotics, and synbiotics. For instance, a recent investigation based on resistant starch suggests that discrete dietary fiber structures can be used to target the production of short-chain fatty acids (1), the major microbiota-derived effector molecules known to have a wide range of action on host health (2). On the other hand, the gut microbiota has been disclosed to modulate the effect of dietary fiber on host health, supporting the notion that there is no one-fits-all diet in the way to seek cost-effective nutritional strategies for health improvement and weight control (3). Anyhow, consensual benefits for human health in microbiota-targeted dietary interventions are still perceived, pointing out, for instance, fermented foods as attenuators of inflammation, and modulators of gut microbiota (4). The aim of the Frontiers in Nutrition Research Topic (RT) “Remodeling Composition and Function of Microbiome by Dietary Strategies—Functional Foods Perspective” was to assemble clinical and pre-clinical studies deciphering the microbiome-driven effects on human health of innovative functional foods based on probiotics, prebiotics or synbiotics, as well as dietary supplements. We provide an overview of this RT, including five original research articles and two review articles.

Background Modern metagenomic analysis of complex microbial communities produces large amounts of sequence data containing information on the microbiome in terms of bacterial, archaeal, viral and eukaryotic composition. The bioinformatics tools available are mainly devoted to profiling the bacterial and viral fractions and only a few software packages consider fungi. As the human fungal microbiome (human mycobiome) can play an important role in the onset and progression of diseases, a comprehensive description of host-microbiota interactions cannot ignore this component. Results HumanMycobiomeScan is a bioinformatics tool for the taxonomic profiling of the mycobiome directly from raw data of next-generation sequencing. The tool uses hierarchical databases of fungi in order to unambiguously assign reads to fungal species more accurately and > 10,000 times faster than other comparable approaches. HumanMycobiomeScan was validated using in silico generated synthetic communities and then applied to metagenomic data, to characterize the intestinal fungal components in subjects adhering to different subsistence strategies. Conclusions Although blind to unknown species, HumanMycobiomeScan allows the characterization of the fungal fraction of complex microbial ecosystems with good performance in terms of sample denoising from reads belonging to other microorganisms. HumanMycobiomeScan is most appropriate for well-studied microbiomes, for which most of the fungal species have been fully sequenced. This released version is functionally implemented to work with human-associated microbiota samples. In combination with other microbial profiling tools, HumanMycobiomeScan is a frugal and efficient tool for comprehensive characterization of microbial ecosystems through shotgun metagenomics sequencing. Electronic supplementary material The online version of this article (10.1186/s12864-019-5883-y) contains supplementary material, which is available to authorized users.

Antibiotic resistance (AR) is indisputably a major health threat which has drawn much attention in recent years. In particular, the gut microbiome has been shown to act as a pool of AR genes, potentially available to be transferred to opportunistic pathogens. Herein, we investigated for the first time changes in the human gut resistome during aging, up to extreme longevity, by analyzing shotgun metagenomics data of fecal samples from a geographically defined cohort of 62 urban individuals, stratified into four age groups: young adults, elderly, centenarians, and semisupercentenarians, i.e., individuals aged up to 109 years. According to our findings, some AR genes are similarly represented in all subjects regardless of age, potentially forming part of the core resistome. Interestingly, aging was found to be associated with a higher burden of some AR genes, including especially proteobacterial genes encoding multidrug efflux pumps. Our results warn of possible health implications and pave the way for further investigations aimed at containing AR accumulation, with the ultimate goal of promoting healthy aging. IMPORTANCE Antibiotic resistance is widespread among different ecosystems, and in humans it plays a key role in shaping the composition of the gut microbiota, enhancing the ecological fitness of certain bacterial populations when exposed to antibiotics. A considerable component of the definition of healthy aging and longevity is associated with the structure of the gut microbiota, and, in this regard, the presence of antibiotic-resistant bacteria is critical to many pathologies that come about with aging. However, the structure of the resistome has not yet been sufficiently elucidated. Here, we show distinct antibiotic resistance assets and specific microbial consortia characterizing the human gut resistome through aging.

Summary In an attempt to explore the role of the gut microbiome during recent canine evolutionary history, we sequenced the metagenome of 13 canine coprolites dated ca. 3,600–3,450 years ago from the Bronze Age archaeological site of Solarolo (Italy), which housed a complex farming community. The microbiome structure of Solarolo dogs revealed continuity with that of modern dogs, but it also shared some features with the wild wolf microbiome, as a kind of transitional state between them. The dietary niche, as also inferred from the microbiome composition, was omnivorous, with evidence of consumption of starchy agricultural foods. Of interest, the Solarolo dog microbiome was particularly enriched in sequences encoding alpha-amylases and complemented a low copy number of the host amylase gene. These findings suggest that Neolithic dogs could have responded to the transition to a starch-rich diet by expanding microbial functionalities devoted to starch catabolism, thus compensating for delayed host response., Graphical abstract, Highlights • Ancient DNA of Bronze Age canine coprolites from Solarolo was sequenced • Solarolo dogs share gut microbiome features with modern wolves and dogs • The gut microbiome of Solarolo dogs shows high number of reads for alpha-amylase • Neolithic canine gut microbiome complemented delay in host genome adaptation, Biological sciences; Microbiome; Evolutionary biology; Evolutionary processes; Phylogenetics; Phylogeny; Evolutionary history; Genomic analysis; Sequence analysis; Omics; Genomics

Multiple sclerosis (MS) is a neurodegenerative inflammatory condition mediated by autoreactive immune processes. Due to its potential to influence host immunity and gut-brain communication, the gut microbiota has been suggested to be involved in the onset and progression of MS. To date, there is no definitive cure for MS, and rehabilitation programs are of the utmost importance, especially in the later stages. However, only a few people generally participate due to poor support, knowledge, and motivation, and no information is available on gut microbiota changes. Herein we evaluated the potential of a brief high-impact multidimensional rehabilitation program (B-HIPE) in a leisure environment to affect the gut microbiota, mitigate MS symptoms and improve quality of life. B-HIPE resulted in modulation of the MS-typical dysbiosis, with reduced levels of pathobionts and the replenishment of beneficial short-chain fatty acid producers. This partial recovery of a eubiotic profile could help counteract the inflammatory tone typically observed in MS, as supported by reduced circulating lipopolysaccharide levels and decreased populations of pro-inflammatory lymphocytes. Improved physical performance and fatigue relief were also found. Our findings pave the way for integrating clinical practice with holistic approaches to mitigate MS symptoms and improve patients’ quality of life.

Despite well-established knowledge of the role of diet and the geographic effect on the gut microbiota of human populations, the temporal dynamics of the individual microbiota profile across changes associated with intercontinental short residence are still far from being understood. This pilot study sought to provide insights into the trajectory of the gut microbiota of an individual during a two-month stay in Italy and a subsequent two-month stay in Nigeria, by 16S rRNA gene sequencing and inferred metagenomics. The gut microbiota underwent massive but temporary changes, both taxonomically and based on predicted functionality. The faecal microbiota associated with the short stay in Italy progressively lost diversity and showed a dominance of Firmicutes, while after returning to Nigeria, the microbial community quickly regained the typical profile, in terms of biodiversity and bacterial signatures of traditional lifestyle, i.e., Prevotella and Treponema. Predicted pathways involved in glycolysis, fermentation and N-acetylneuraminate degradation were enriched during the subsequent two-month stay in Nigeria, whereas pathways associated with amino acid and peptidoglycan synthesis and maturation became over-represented during short stay in Italy. Our findings stress the plasticity of the individual gut microbiota even during a short-term travel, with loss/gain of taxonomic and functional features that mirror those of the gut microbiota of indigenous people dwelling therein.

Deep learning methodologies have revolutionized prediction in many fields and show the potential to do the same in microbial metagenomics. However, deep learning is still unexplored in the field of microbiology, with only a few software designed to work with microbiome data. Within the meta-community theory, we foresee new perspectives for the development and application of deep learning algorithms in the field of the human microbiome. In this context, we developed G2S, a bioinformatic tool for taxonomic prediction of the human fecal microbiome directly from the oral microbiome data of the same individual. The tool uses a deep convolutional neural network trained on paired oral and fecal samples from populations across the globe, which allows inferring the stool microbiome at the family level more accurately than other available approaches. The tool can be used in retrospective studies, where fecal sampling was not performed, and especially in the field of paleomicrobiology, as a unique opportunity to recover data related to ancient gut microbiome configurations. G2S was validated on already characterized oral and fecal sample pairs, and then applied to ancient microbiome data from dental calculi, to derive putative intestinal components in medieval subjects.

The microbiota–gut–brain axis extends beyond visceral perception, influencing higher-order brain structures, and ultimately psychological functions, such as fear processing. In this exploratory pilot study, we attempted to provide novel experimental evidence of a relationship between gut microbiota composition and diversity, and fear-processing in obesity, through a behavioral approach. Women affected by obesity were enrolled and profiled for gut microbiota, through 16S rRNA amplicon sequencing. Moreover, we tested their ability to recognize facial fearful expressions through an implicit-facial-emotion-recognition task. Finally, a traditional self-report questionnaire was used to assess their temperamental traits. The participants exhibited an unbalanced gut microbiota profile, along with impaired recognition of fearful expressions. Interestingly, dysbiosis was more severe in those participants with altered behavioral performance, with a decrease in typically health-associated microbes, and an increase in the potential pathobiont, Collinsella. Moreover, Collinsella was related to a lower expression of the persistence temperamental trait, while a higher expression of the harm-avoidance temperament, related to fear-driven anxiety symptoms, was linked to Lactobacillus. Once confirmed, our findings could pave the way for the design of innovative microbiome-based strategies for the treatment of psychological and emotional difficulties by mitigating obesity-related consequences and behaviors.

Respiratory tract infections (RTIs) are common in childhood and represent one of the main causes of hospitalization in this population. In recent years, many studies have described the association between gut microbiota (GM) composition and RTIs in animal models. In particular, the “inter-talk” between GM and the immune system has recently been unveiled. However, the role of GM in human, and especially infantile, RTIs has not yet been fully established. In this narrative review we provide an up-to-date overview of the physiological pathways that explain how the GM shapes the immune system, potentially influencing the response to common childhood respiratory viral infections and compare studies analysing the relationship between GM composition and RTIs in children. Most studies provide evidence of GM dysbiosis, but it is not yet possible to identify a distinct bacterial signature associated with RTI predisposition. A better understanding of GM involvement in RTIs could lead to innovative integrated GM-based strategies for the prevention and treatment of RTIs in the paediatric population.

The SARS-CoV-2-associated COVID-19 pandemic has shaken the global healthcare system. Although the best-known symptoms are dry cough and pneumonia, viral RNA has been detected in the stool and about half of COVID-19 patients exhibit gastrointestinal upset. In this scenario, special attention is being paid to the possible role of the gut microbiota (GM). Fecal samples from 69 COVID-19 patients from three different hospitals of Bologna (Italy) were analyzed by 16S rRNA gene-based sequencing. The GM profile was compared with the publicly available one of healthy age- and gender-matched Italians, as well as with that of other critically ill non-COVID-19 patients. The GM of COVID-19 patients appeared severely dysbiotic, with reduced diversity, loss of health-associated microorganisms and enrichment of potential pathogens, particularly Enterococcus. This genus was far overrepresented in patients developing bloodstream infections (BSI) and admitted to the intensive care unit, while almost absent in other critically ill non-COVID-19 patients. Interestingly, the percentage of patients with BSI due to Enterococcus spp. was significantly higher during the COVID-19 pandemic than in the previous 3 years. Monitoring the GM of critically ill COVID-19 patients could help clinical management, by predicting the onset of medical complications such as difficult-to-treat secondary infections.

Increasing evidence indicates that host-associated microbial communities play a key role in the biology of marine eukaryotic organisms. Amongst them, Corallimorpharia are extensively found on reefs, carpeting vast reef areas, where they can exert important roles as habitat forming holobionts, being at the base of complex trophic webs. Here we explore the bacterial community structure, and its changes across different seasons, associated with the jewel anemone Corynactis viridis, an anthozoan Cnidaria that is widely distributed in the northeastern Atlantic Ocean and the Mediterranean Sea. Samples were collected in the North Adriatic Sea in three seasons and the community composition was studied using 16S rDNA sequencing. We show that C. viridis-associated microbial communities are unique and significantly different from those in the surrounding seawater. Interestingly, we observe remarkable changes in the C. viridis microbiome according to seasonality. In particular, the C. viridis microbiome is capable of rearranging its overall ecological structure with the winter-summer transition, moving from an oligotrophic anaerobic community to a heterotrophic ecosystem, with the propensity to ferment proteins and complex polysaccharides. Our findings demonstrate that C. viridis has a unique associated microbiota and suggest that this is capable of adapting to seasonal changes in the host physiology, by establishing a microbiome-host interaction process whose relevance to C. viridis has yet to be determined.

The disruption of gut microbiota eubiosis has been linked to major complications in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Various strategies have been developed to reduce dysbiosis and related complications. Fecal microbiota transplantation (FMT) consists of the infusion of fecal matter from a healthy donor to restore impaired intestinal homeostasis, and could be applied in the allo-HSCT setting. We conducted a systematic review of studies addressing the use of FMT in allo-HSCT patients. In the 23 papers included in the qualitative synthesis, FMT was used for the treatment of recurrent Clostridioides difficile infections or as a therapeutic strategy for steroid-resistant gut aGvHD. FMT was also performed with a preventive aim (e.g., to decolonize from antibiotic-resistant bacteria). Additional knowledge on the biological mechanisms underlying clinical findings is needed in order to employ FMT in clinical practice. There is also concern regarding the administration of microbial consortia in immune-compromised patients with altered gut permeability. Therefore, the safety profile and efficacy of the procedure must be determined to better assess the role of FMT in allo-HSCT recipients.

Background: Osteoarthritis (OA) is the most common form of chronic pain in Europe (34%), representing a great economic and social cost to society. There are studies that suggest an intestine–brain–articulation axis and hint at the existence of low-grade intestinal inflammation in OA, which would be related to an alteration of the microbiota and to the impairment of the epithelial barrier, with leakage of the microbial components. Purpose: The purpose of this study was to review the association between gut microbiome and pain in the OA population through a review of the literature. Methods: A literature search was conducted to identify all available studies on the association between the gut microbiome and pain in the OA population, with no publication date limit until September 2020 and no language limit, in the MEDLINE, CINAHL, Web of Science and Cochrane Central Register of Controlled Trials databases. Results: Only three of 2084 studies detected and analyzed by performing the proposed searches in the detailed databases, were finally selected for this review, of which one was with and two were without intervention. These studies only weakly support a relationship between the gut microbiome and OA, specifically a correlation between certain taxa or microbial products and the inflammatory landscape and severity of OA symptoms, including knee pain. Conclusions: Despite encouraging results, this review highlights the paucity of high-quality studies addressing the potential role of the gut microbiome in OA-related pain, along with the disparity of the techniques used so far, making it impossible to draw firm conclusions on the topic.

The gut microbiome has emerged as a major character in the context of hematopoietic stem cell transplantation. The biology underpinning this relationship is still to be defined. Recently, mounting evidence has suggested a role for microbiome-derived metabolites in mediating crosstalk between intestinal microbial communities and the host. Some of these metabolites, such as fiber-derived short-chain fatty acids or amino acid-derived compounds, were found to have a role also in the transplant setting. New interesting data have been published on this topic, posing a new intriguing perspective on comprehension and treatment. This review provides an updated comprehensive overview of the available evidence in the field of gut microbiome-derived metabolites and hematopoietic stem cell transplantation.

Diet is a major driver of gut microbiota variation and plays a role in metabolic disorders, including metabolic syndrome (MS). Mycorrhized foods from symbiotic agriculture (SA) exhibit improved nutritional properties, but potential benefits have never been investigated in humans. We conducted a pilot interventional study on 60 adults with ≥ 1 risk factors for MS, of whom 33 consumed SA-derived fresh foods and 27 received probiotics over 30 days, with a 15-day follow-up. Stool, urine and blood were collected over time to explore changes in gut microbiota, metabolome, and biochemical, inflammatory and immunologic parameters, previous dietary habits were investigated through a validated food-frequency questionnaire. The baseline microbiota showed alterations typical of metabolic disorders, mainly an increase in Coriobacteriaceae and a decrease in health-associated taxa, which were partly reversed after the SA-based diet. Improvements were observed in metabolome, MS presence (two out of six subjects no longer had MS) or components. Changes were more pronounced with less healthy baseline diets. Probiotics had a marginal, not entirely favorable, effect, although one out of three subjects no longer suffered from MS. These findings suggest that improved dietary patterns can modulate the host microbiota and metabolome, counteracting the risk of developing MS.

Hepatic sinusoidal obstruction syndrome (SOS/VOD) represents a dramatic complication of hematopoietic stem cell transplantation (HSCT), particularly in children. Recent evidence has suggested a role for the gut microbiome (GM) in the context of HSCT and its related complications, but no data are available on the relationship between GM and SOS/VOD. Here, we conducted a retrospective case–control study in allo-HSCT pediatric patients developing or not SOS/VOD and profiled their GM over time, from before the transplant up to 72 days after. A rich and diverse GM before HSCT was found to be associated with a reduced likelihood of developing SOS/VOD. Furthermore, prior to transplant, patients not developing SOS/VOD showed an enrichment in some typically health-associated commensals, such as Bacteroides, Ruminococcaceae and Lachnospiraceae. Their levels remained overall higher until post-transplant. This high-diversity configuration resembles that described in other studies for other HSCT-related complications, including graft-versus-host disease, potentially representing a common protective GM feature against HSCT complications.

Background and Objectives: Maturation of the gut microbiota (GM) in infants is critically affected by environmental factors, with potential long-lasting clinical consequences. Continuous low-dose antibiotic prophylaxis (CAP) is the standard of care for children with vesicoureteral reflux (VUR), in order to prevent recurrent urinary tract infections. We aimed to assess short-term GM modifications induced by CAP in infants. Methods: We analyzed the GM structure in 87 infants (aged 1-5 months) with high-grade VUR, previously exposed or naïve to CAP. Microbial DNA was extracted from stool samples. GM profiling was achieved by 16S rRNA gene-based next-generation sequencing. Fecal levels of short- and branched-chain fatty acids were also assessed. Results: 36/87 patients had been taking daily CAP for a median time of 47 days, while 51/87 had not. In all patients, the GM was predominantly composed by Bifidobacteriaceae and Enterobacteriaceae. Subgroup comparative analysis revealed alterations in the GM composition of CAP-exposed infants at phylum, family and genus level. CAP-exposed GM was enriched in members of Enterobacteriaceae and Bacteroidetes, especially in the genera Bacteroides and Parabacteroides, and showed a trend toward increased Klebsiella, often associated with antibiotic resistance. In contrast, the GM of non-CAP children was mostly enriched in Bifidobacterium. No differences were found in fatty acid levels. Conclusions: In infants with VUR, even a short exposure to CAP definitely alters the GM composition, with increased relative abundance of opportunistic pathogens and decreased proportions of health-promoting taxa. Early low-dose antibiotic exposure might bear potential long-term clinical risks. ispartof: FRONTIERS IN PEDIATRICS vol:9 ispartof: location:Switzerland status: published

Recent pieces of evidence have emerged on the relevance of microorganisms in modulating responses to anticancer treatments and reshaping the tumor-immune microenvironment. On the one hand, many studies have addressed the role of the gut microbiota, providing interesting correlative findings with respect to etiopathogenesis and treatment responses. On the other hand, intra-tumoral bacteria are being recognized as intrinsic and essential components of the cancer microenvironment, able to promote a plethora of tumor-related aspects from cancer growth to resistance to chemotherapy. These elements will be probably more and more valuable in the coming years in early diagnosis and risk stratification. Furthermore, microbial-targeted intervention strategies may be used as adjuvants to current therapies to improve therapeutic responses and overall survival. This review focuses on new insights and therapeutic approaches that are dawning against pancreatic cancer: a neoplasm that arises in a central metabolic “hub” interfaced between the gut and the host.

After spinal cord injury (SCI), patients face many physical and psychological issues including intestinal dysfunction and comorbidities, strongly affecting quality of life. The gut microbiota has recently been suggested to influence the course of the disease in these patients. However, to date only two studies have profiled the gut microbiota in SCI patients, months after a traumatic injury. Here we characterized the gut microbiota in a large Italian SCI population, within a short time from a not only traumatic injury. Feces were collected within the first week at the rehabilitation center (no later than 60 days after SCI), and profiled by 16S rRNA gene-based next-generation sequencing. Microbial profiles were compared to those publicly available of healthy age- and gender-matched Italians, and correlated to patient metadata, including type of SCI, spinal unit location, nutrition and concomitant antibiotic therapies. The gut microbiota of SCI patients shows distinct dysbiotic signatures, i.e. increase in potentially pathogenic, pro-inflammatory and mucus-degrading bacteria, and depletion of short-chain fatty acid producers. While robust to most host variables, such dysbiosis varies by lesion level and completeness, with the most neurologically impaired patients showing an even more unbalanced microbial profile. The SCI-related gut microbiome dysbiosis is very likely secondary to injury and closely related to the degree of completeness and severity of the lesion, regardless of etiology and time interval. This microbial layout could variously contribute to increased gut permeability and inflammation, potentially predisposing patients to the onset of severe comorbidities.

Gastric cancer (GC) is the fifth most prevalent cancer worldwide and the third leading cause of global cancer mortality. With the advances of the omic studies, a heterogeneous GC landscape has been revealed, with significant molecular diversity. Given the multifaceted nature of GC, identification of different patient subsets with prognostic and/or predictive outcomes is a key aspect to allow tailoring of specific treatments. Recently, the involvement of the microbiota in gastric carcinogenesis has been described. To deepen this aspect, we compared microbiota composition in signet-ring cell carcinoma (SRCC) and adenocarcinoma (ADC), two distinct GC subtypes. To this purpose, 10 ADC and 10 SRCC and their paired non-tumor (PNT) counterparts were evaluated for microbiota composition through 16S rRNA analysis. Weighted and unweighted UniFrac and Bray&ndash, Curtis dissimilarity showed significant community-level separation between ADC and SRCC. Through the LEfSe (linear discriminant analysis coupled with effect size) tool, we identified potential microbial biomarkers associated with GC subtypes. In particular, SRCCs were significantly enriched in the phyla Fusobacteria, Bacteroidetes, Patescibacteria, whereas in the ADC type, Proteobacteria and Acidobacteria phyla were found. Overall, our data add new insights into GC heterogeneity and may contribute to deepening the GC classification.

Nutritional support for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been widely debated. Enteral nutrition (EN) is recommended as first-line nutritional support by the main international guidelines. However, these recommendations are based on weak evidence, and there is wide variability in the types of nutritional support among transplantation centers, with the majority providing parenteral nutrition (PN) instead of EN. Here we provide an up-to-date systematic review and meta-analysis of studies comparing EN and PN for nutritional support during the neutropenic period after allo-HSCT. The literature search strategy identified 13 papers, of which 10 compared clinical transplantation outcomes, 2 compared gut microbiota (GM) compositions, and 1 compared systemic metabolic profiles. For the meta-analysis, among the 10 clinical studies, 8 studies in which 2 groups were compared were selected: in 1 group, EN was provided as primary nutritional support in the neutropenic phase after allo-HSCT with or without the addition of PN (EN group), whereas in the other group, only PN was provided as nutritional support. The incidence rates of acute graft-versus-host disease (aGVHD) (relative risk [RR], 0.69; 95% confidence interval [CI], 0.56 to 0.86; P = .0007), aGVHD grade III-IV (RR, 0.44; 95% CI, 0.30 to 0.64; P < .0001), and gut aGVHD (RR, 0.44; 95% CI, 0.30 to 0.66; P < .0001) were lower in the EN group than in the PN group. No differences were found between the 2 groups with regard to the incidence of severe oral mucositis (RR, 0.95; 95% CI, 0.83 to 1.09; P = .46) or overall survival at day +100 (RR, 1.07; 95% CI, 0.95 to 1.21; P = .29). Other variables were too heterogeneous to perform quantitative analyses. The results of the meta-analysis showed that EN reduced the incidence of aGVHD, specifically grade III-IV and gut aGVHD. This result should prompt improved efforts to implement EN as first-line nutritional support in patients undergoing allo-HSCT. Considering the emerging evidence regarding the association between GM dysbiosis and aGVHD onset, we speculate that this protective effect could be attributed to the improved gut eubiosis observed in enterally fed patients. Further studies are warranted to better address the relationship between the GM composition, aGVHD, and the nutritional administration route during HSCT.

The gut microbiome (GM) has been associated with different clinical outcomes in the context of allogeneic hematopoietic stem cell transplantation (HSCT). Large multicenter cohort studies in adults have found significant correlations with overall survival, relapse, and incidence of complications. Moreover, GM is already a promising target for therapeutic interventions. However, few data are available in children, a population presenting unique features and challenges. During childhood, the GM evolves rapidly with large structural fluctuations, alongside with the maturation of the immune system. Furthermore, the HSCT procedure presents significant differences in children. These considerations underline the importance of a specific focus on the pediatric setting, and the role of GM and its age-dependent trajectory in influencing the immunity reconstitution and clinical outcomes. This review provides a comprehensive overview of the available evidence in the field of GM and pediatric HSCT, highlighting age-specific issues and discussing GM-based therapeutic approaches.

International audience; The upcoming exploration missions will imply a much longer duration than any of the missions flown so far. In these missions, physiological adaptation to the new environment leads to changes in different body systems, such as the cardiovascular and musculoskeletal systems, metabolic and neurobehavioral health and immune function. To keep space travelers healthy on their trip to Moon, Mars and beyond and their return to Earth, a variety of countermeasures need to be provided to maintain body functionality. From research on the International Space Station (ISS) we know today, that for instance prescribing an adequate training regime for each individual with the devices available in the respective spacecraft is still a challenge. Nutrient supply is not yet optimal and must be optimized in exploration missions. Food intake is intrinsically linked to changes in the gut microbiome composition. Most of the microbes that inhabit our body supply ecosystem benefit to the host-microbe system, including production of important resources, bioconversion of nutrients, and protection against pathogenic microbes. The gut microbiome has also the ability to signal the host, regulating the processes of energy storage and appetite perception, and influencing immune and neurobehavioral function. The composition and functionality of the microbiome most likely changes during spaceflight. Supporting a healthy microbiome by respective measures in space travelers might maintain their health during the mission but also support rehabilitation when being back on Earth. In this review we are summarizing the changes in the gut microbiome observed in spaceflight and analog models, focusing particularly on the effects on metabolism, the musculoskeletal and immune systems and neurobehavioral disorders. Since space travelers are healthy volunteers, we focus on the potential of countermeasures based on pre- and probiotics supplements.

Background: Butyric acid (BA) is a short-chain fatty acid (SCFA) with anti-inflammatory properties, which promotes intestinal barrier function. Medium-chain fatty acids (MCFA), including caproic acid (CA), promote TH1 and TH17 differentiation, thus supporting inflammation. Aim: Since most SCFAs are absorbed in the cecum and colon, the measurement of BA in peripheral blood could provide information on the health status of the intestinal ecosystem. Additionally, given the different immunomodulatory properties of BA and CA the evaluation of their serum concentration, as well as their ratio could be as a simple and rapid biomarker of disease activity and/or treatment efficacy in MS. Methods: We evaluated serum BA and CA concentrations, immune parameters, intestinal barrier integrity and the gut microbiota composition in patients with multiple sclerosis (MS) comparing result to those obtained in healthy controls. Results: In MS, the concentration of BA was reduced and that of CA was increased. Concurrently, the microbiota was depleted of BA producers while it was enriched in mucin-degrading, pro-inflammatory components. The reduced serum concentration of BA seen in MS patients correlated with alterations of the barrier permeability, as evidenced by the higher plasma concentrations of lipopolysaccharide and intestinal fatty acid-binding protein, and inflammation. Specifically, CA was positively associated with CD4+/IFNγ+ T lymphocytes, and the BA/CA ratio correlated positively with CD4+/CD25high/Foxp3+ and negatively with CD4+/IFNγ+ T lymphocytes. Conclusion: The gut microbiota dysbiosis found in MS is possibly associated with alterations of the SCFA/MCFA ratio and of the intestinal barrier; this could explain the chronic inflammation that characterizes this disease. SCFA and MCFA quantification could be a simple biomarker to evaluate the efficacy of therapeutic and rehabilitation procedures in MS.

The study of longevity may help us understand how human beings can delay or survive the most frequent age-related diseases and morbidities. In this scenario, the gut microbiome has been proposed as one of the variables to monitor and possibly support healthy aging. Indeed, the disruption of host-gut microbiome homeostasis has been associated with inflammation and intestinal permeability as well as a general decline in bone and cognitive health. Here, we performed a metagenomic assessment of fecal samples from semisupercentenarians, i.e., 105 to 109 years old, in comparison to young adults, the elderly, and centenarians, shedding light on the longest compositional and functional trajectory of the human gut microbiome with aging. In addition to providing a fine taxonomic resolution down to the species level, our study emphasizes the progressive age-related increase in degradation pathways of pervasive xenobiotics in Western societies, possibly as a result of a supportive process within the molecular continuum characterizing aging., The gut microbiome of long-lived people display an increasing abundance of subdominant species, as well as a rearrangement in health-associated bacteria, but less is known about microbiome functions. In order to disentangle the contribution of the gut microbiome to the complex trait of human longevity, we here describe the metagenomic change of the human gut microbiome along with aging in subjects with up to extreme longevity, including centenarians (aged 99 to 104 years) and semisupercentenarians (aged 105 to 109 years), i.e., demographically very uncommon subjects who reach the extreme limit of the human life span. According to our findings, the gut microbiome of centenarians and semisupercentenarians is more suited for xenobiotic degradation and shows a rearrangement in metabolic pathways related to carbohydrate, amino acid, and lipid metabolism. Collectively, our data go beyond the relationship between intestinal bacteria and physiological changes that occur with aging by detailing the shifts in the potential metagenomic functions of the gut microbiome of centenarians and semisupercentenarians as a response to progressive dietary and lifestyle modifications. IMPORTANCE The study of longevity may help us understand how human beings can delay or survive the most frequent age-related diseases and morbidities. In this scenario, the gut microbiome has been proposed as one of the variables to monitor and possibly support healthy aging. Indeed, the disruption of host-gut microbiome homeostasis has been associated with inflammation and intestinal permeability as well as a general decline in bone and cognitive health. Here, we performed a metagenomic assessment of fecal samples from semisupercentenarians, i.e., 105 to 109 years old, in comparison to young adults, the elderly, and centenarians, shedding light on the longest compositional and functional trajectory of the human gut microbiome with aging. In addition to providing a fine taxonomic resolution down to the species level, our study emphasizes the progressive age-related increase in degradation pathways of pervasive xenobiotics in Western societies, possibly as a result of a supportive process within the molecular continuum characterizing aging.

Background Dietary lignans belong to the group of phytoestrogens together with coumestans, stilbenes and isoflavones, and themselves do not exhibit oestrogen-like properties. Nonetheless, the gut microbiota converts them into enterolignans, which show chemical similarity to the human oestrogen molecule. One of the richest dietary sources of lignans are oilseeds, including flaxseed. The aim of this pilot study was to determine the concentration of the main dietary lignans in an oilseed mix, and explore the gut microbiota-dependent production of enterolignans for oestrogen substitution in young and premenopausal women. The oilseed mix was fermented in a pH-controlled batch culture system inoculated with women’s faecal samples. The lignan content and enterolignan production were measured by ultra‐high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS), and the faecal-derived microbial communities were profiled by 16S rRNA gene-based next-generation sequencing. Results In vitro batch culture fermentation of faecal samples inoculated with oilseed mix for 24 h resulted in a substantial increase in enterolactone production in younger women and an increase in enterodiol in the premenopausal group. As for the gut microbiota, different baseline profiles were observed as well as different temporal dynamics, mainly related to Clostridiaceae, and Klebsiella and Collinsella spp. Conclusions Despite the small sample size, our pilot study revealed that lignan-rich oilseeds could strongly influence the faecal microbiota of both younger and premenopausal females, leading to a different enterolignan profile being produced. Further studies in larger cohorts are needed to evaluate the long-term effects of lignan-rich diets on the gut microbiota and find out how enterolactone-producing bacterial species could be increased. Diets rich in lignans could potentially serve as a safe supplement of oestrogen analogues to meet the cellular needs of endogenous oestrogen and deliver numerous health benefits, provided that the premenopausal woman microbiota is capable of converting dietary precursors into enterolignans.

Kawasaki disease (KD) and Henoch–Schönlein purpura (HSP) are the most frequent vasculitis in childhood. For both, a multifactorial mechanism has been hypothesised, with an abnormal immune response in genetically predisposed children. Gut microbiota (GM) alterations might trigger the hyperimmune reaction. Our aim was to explore the GM in KD and compare it with the GM of HSP and febrile children. Children diagnosed with KD, HSP and non-KD febrile illness (F) were enrolled. GM was profiled by 16S rRNA gene sequencing and compared with the profiles of healthy children from previous studies. We enrolled 13 KD, 10 HSP and 12 F children. Their GM significantly differed from controls, with an overall reduction in the relative abundance of beneficial taxa belonging to the Ruminococcaceae and Lachnospiraceae families. Potential KD and HSP signatures were identified, including smaller amounts of Dialister in the former, and Clostridium and Akkermansia in the latter. Notably, the GM structures of KD, HSP and F patients stratified by abdominal involvement, with more severe dysbiosis in those suffering from intestinal symptoms. This is the first study analysing GM in a mostly Caucasian cohort of KD and HSP children. Our data could open up new opportunities for childhood vasculitis treatment.

Simple Summary Patients with polycythemia vera, a myeloproliferative neoplasm, are at increased risk of thrombosis and progression to myelofibrosis. However, no disease-specific risk factors have been identified so far. Extracellular vesicles, released from a broad variety of cells, are receiving increasing attention for their effects on cell-to-cell communication. In addition, they play a role in cancer and thrombosis. Interestingly, circulating microbial components/microbes have been recently indicated as potential modifiers of inflammation and coagulation. Here, we identified a signature of thrombosis history and marrow fibrosis by analyzing the phenotype and the microbial DNA cargo of the circulating extracellular vesicles after isolation from the plasma of patients with polycythemia vera. These data may support the role of extracellular vesicles as liquid biomarkers of aggressive disease, thus contributing to refining the prognosis of polycythemia vera. Abstract Polycythemia vera is a myeloproliferative neoplasm with increased risk of thrombosis and progression to myelofibrosis. However, no disease-specific risk factors have been identified so far. Circulating extracellular vesicles (EVs) are mostly of megakaryocyte (MK-EVs) and platelet (PLT-EVs) origin and, along with phosphatidylethanolamine (PE)-EVs, play a role in cancer and thrombosis. Interestingly, circulating microbial components/microbes have been recently indicated as potential modifiers of inflammation and coagulation. Here, we investigated phenotype and microbial DNA cargo of EVs after isolation from the plasma of 38 patients with polycythemia vera. Increased proportion of MK-EVs and reduced proportion of PLT-EVs identify patients with thrombosis history. Interestingly, EVs from patients with thrombosis history were depleted in Staphylococcus DNA but enriched in DNA from Actinobacteria members as well as Anaerococcus. In addition, patients with thrombosis history had also lower levels of lipopolysaccharide-associated EVs. In regard to fibrosis, along with increased proportion of PE-EVs, the EVs of patients with marrow fibrosis were enriched in DNA from Collinsella and Flavobacterium. Here, we identified a polycythemia-vera-specific host/microbial EV-based signature associated to thrombosis history and marrow fibrosis. These data may contribute to refining PV prognosis and to identifying novel druggable targets.

Immunosenescence is marked by a systemic process named inflammaging along with a series of defects in the immunological activity that results in poor responses to infectious agents and to vaccination. Inflammaging, a state of low-grade chronic inflammation, usually leads to chronic inflammatory diseases and frailty in the elderly. However, some elderly escape from frailty and reach advanced age free of the consequences of inflammaging. This process has been called immunological remodeling, and it is the hallmark of healthy aging as described in the studies of centenarians in Italy. The biological markers of healthy aging are still a matter of debate, and the studies on the topic have focused on inflammatory versus remodeling processes and molecules. The sub-clinical inflammatory status associated with aging might be a deleterious event for populations living in countries where chronic infectious diseases are not prevalent. Nevertheless, in other parts of the world where they are, two possibilities may occur. Inflammatory responses may have a protective effect against these infectious agents. At the same time, the long-term consequences of protective immune responses during chronic infections may result in accelerated immunosenescence in these individuals. Therefore, the biological markers of healthy aging can vary according to environmental, cultural, and geographical settings that reflect worldwide, and in a non-biased, non-westernized perspective, the changes that we experience regarding our contacts with microorganisms and the outcomes of such contacts.

Hypertension is a major global health challenge, as it represents the main risk factor for stroke and cardiovascular disease. It is a multifactorial clinical condition characterized by high and sustained levels of blood pressure, likely resulting from a complex interplay of endogenous and environmental factors. The gut microbiota has been strongly supposed to be involved but its role in hypertension is still poorly understood. In an attempt to fill this gap, here we characterized the microbial composition of fecal samples from 48 hypertensive and 32 normotensive Brazilian individuals by next-generation sequencing of the 16S rRNA gene. In addition, the cytokine production of peripheral blood samples was investigated to build an immunological profile of these individuals. We identified a dysbiosis of the intestinal microbiota in hypertensive subjects, featured by reduced biodiversity and distinct bacterial signatures compared with the normotensive counterpart. Along with a reduction in Bacteroidetes members, hypertensive individuals were indeed mainly characterized by increased proportions of Lactobacillus and Akkermansia while decreased relative abundances of well-known butyrate-producing commensals, including Roseburia and Faecalibacterium within the Lachnospiraceae and Ruminococcaceae families. We also observed an inflamed immune profile in hypertensive individuals with an increase in TNF/IFN-γ ratio, and in TNF and IL-6 production when compared to normotensive ones. Our work provides the first evidence of association of hypertension with altered gut microbiota and inflammation in a Brazilian population. While lending support to the existence of potential microbial signatures of hypertension, likely to be robust to age and geography, our findings point to largely neglected bacteria as potential contributors to intestinal homeostasis loss and emphasize the high vulnerability of hypertensive individuals to inflammation-related disorders.

Coral microbiomes, the complex microbial communities associated with the different anatomic compartments of the coral, provide important functions for the host's survival, such as nutrient cycling at the host's surface, prevention of pathogens colonization, and promotion of nutrient uptake. Microbiomes are generally referred to as plastic entities, able to adapt their composition and functionality in response to environmental change, with a possible impact on coral acclimatization to phenomena related to climate change, such as ocean acidification. Ocean sites characterized by natural gradients of pCO2 provide models for investigating the ability of marine organisms to acclimatize to decreasing seawater pH. Here we compared the microbiome of the temperate, shallow water, non-symbiotic solitary coral Astroides calycularis that naturally lives at a volcanic CO2 vent in Ischia Island (Naples, Italy), with that of corals living in non-acidified sites at the same island. Bacterial DNA associated with the different anatomic compartments (mucus, tissue and skeleton) of A. calycularis was differentially extracted and a total of 68 samples were analyzed by 16S rRNA gene sequencing. In terms of phylogenetic composition, the microbiomes associated with the different coral anatomic compartments were different from each other and from the microbial communities of the surrounding seawater. Of all the anatomic compartments, the mucus-associated microbiome differed the most between the control and acidified sites. The differences detected in the microbial communities associated to the three anatomic compartments included a general increase in subdominant bacterial groups, some of which are known to be involved in different stages of the nitrogen cycle, such as potential nitrogen fixing bacteria and bacteria able to degrade organic nitrogen. Our data therefore suggests a potential increase of nitrogen fixation and recycling in A. calycularis living close to the CO2 vent system.

Background Behçet’s syndrome (BS) is a systemic inflammatory disorder of unknown etiology, and it is characterized by a wide range of potential clinical manifestations. Recent evidence suggests that the gut microbiota (GM) in BS has low biodiversity with a significant depletion in butyrate producers. The aim of the present project is to investigate whether a dietary intervention could ameliorate the clinical manifestations and modulate the GM of individuals with BS. Methods This is a randomized, open, cross-over study that involves 90 individuals with BS, who will be randomly assigned to one of three different diets for 3 months: a lacto-ovo-vegetarian diet (VD), a Mediterranean diet (MD), or a Mediterranean diet supplemented with butyrate (MD-Bt). The VD will contain inulin-resistant and resistant-starch-rich foods, eggs, and dairy in addition to plant-based food, but it will not contain meat, poultry, or fish. The MD will contain all food categories and will provide two portions per week of fish and three portions per week of fresh and processed meat. The MD-Bt will be similar to the MD but supplemented with 1.8 g/day of oral butyrate. The three different diets will be isocaloric and related to the participants’ nutritional requirements. Anthropometric measurements, body composition, blood, and fecal samples will be obtained from each participant at the beginning and the end of each intervention phase. The primary outcomes will be represented by the change from baseline of the BS gastrointestinal and systemic symptoms. Changes from baseline in GM composition, short-chain fatty acid (SCFA) production, and the inflammatory and antioxidant profile will be considered as secondary outcomes. Discussion BS is a rare disease, and, actually, not all the available treatments are target therapies. A supportive treatment based on dietary and lifestyle issues, able to restore immune system homeostasis, could have a high impact on cost sustainability for the treatment of such a chronic and disabling inflammatory condition. Trial registration clinicaltrials.gov: NCT03962335. Registered on 21 May 2019.

Hematopoietic stem cell transplantation (HSCT) is the first-line immunotherapy to treat several hematologic disorders, although it can be associated with many complications reducing the survival rate, such as acute graft-versus-host disease (aGvHD) and infections. Given the fundamental role of the gut microbiome (GM) for host health, it is not surprising that a suboptimal path of GM recovery following HSCT may compromise immune homeostasis and/or increase the risk of opportunistic infections, with an ultimate impact in terms of aGvHD onset. Traditionally, the first nutritional approach in post-HSCT patients is parenteral nutrition (PN), which is associated with several clinical adverse effects, supporting enteral nutrition (EN) as a preferential alternative. The aim of the study was to evaluate the impact of EN vs. PN on the trajectory of compositional and functional GM recovery in pediatric patients undergoing HSCT. The GM structure and short-chain fatty acid (SCFA) production profiles were analyzed longitudinally in twenty pediatric patients receiving HSCT&mdash, of which, ten were fed post-transplant with EN and ten with total PN. According to our findings, we observed the prompt recovery of a structural and functional eubiotic GM layout post-HSCT only in EN subjects, thus possibly reducing the risk of systemic infections and GvHD onset.

Accumulating literature is providing evidence that the gut microbiota is involved in metabolic disorders, but the question of how to effectively modulate it to restore homeostasis, especially in the elderly, is still under debate. In this study, we profiled the intestinal microbiota of 20 elderly obese women (EO) at the baseline (T0), after 15 days of hypocaloric Mediterranean diet administered as part of a nutritional-metabolic rehabilitation program for obesity (T1), and after a further 15 days of the same diet supplemented with a probiotic mix (T2). Fecal samples were characterized by Illumina MiSeq sequencing of the 16S rRNA gene. The EO microbiota showed the typical alterations found in obesity, namely, an increase in potential pro-inflammatory components (i.e., Collinsella) and a decrease in health-promoting, short-chain fatty acid producers (i.e., Lachnospiraceae and Ruminococcaceae members), with a tendency to reduced biodiversity. After 15 days of the rehabilitation program, weight decreased by (2.7 &plusmn, 1.5)% and the gut microbiota dysbiosis was partially reversed, with a decline of Collinsella and an increase in leanness-related taxa. During the next 15 days of diet and probiotics, weight dropped further by (1.2 &plusmn, 1.1)%, markers of oxidative stress improved, and Akkermansia, a mucin degrader with beneficial effects on host metabolism, increased significantly. These findings support the relevant role of a correct dietetic approach, even in the short term, to modulate the EO gut microbiota towards a metabolic health-related configuration, counteracting the increased risk of morbidity in these patients.

Background Advances in bioinformatics recently allowed for the recovery of ‘metagenomes assembled genomes’ from human microbiome studies carried on with shotgun sequencing techniques. Such approach is used as a mean to discover new unclassified metagenomic species, putative biological entities having distinct metabolic traits. Results In the present analysis we compare 400 genomes from isolates available on NCBI database and 10,000 human gut metagenomic species, screening all of them for the presence of a minimal set of core functionalities necessary, but not sufficient, for life. As a result, the metagenome-assembled genomes resulted systematically depleted in genes encoding for essential functions apparently needed to support autonomous bacterial life. Conclusions The relevant degree of lacking core functionalities that we observed in metagenome-assembled genomes raises some concerns about the effective completeness of metagenome-assembled genomes, suggesting caution in extrapolating biological information about their metabolic propensity and ecology in a complex environment like the human gastrointestinal tract.

The gut microbiome of pediatric patients undergoing allo-hematopoietic stem cell transplantation (HSCT) has recently been considered as a potential reservoir of antimicrobial resistance, with important implications in terms of patient mortality rate. By means of shotgun metagenomics, here we explored the dynamics of the gut resistome – i.e. the pattern of antibiotic resistance genes provided by the gut microbiome – in eight pediatric patients undergoing HSCT, half of whom developed acute Graft-versus-Host Disease (aGvHD). According to our findings, the patients developing aGvHD are characterized by post-HSCT expansion of their gut resistome, involving the acquisition of new resistances, as well as the consolidation of those already present before HSCT. Interestingly, the aGvHD-associated bloom in resistome diversity is not limited to genes coding for resistance to the antibiotics administered along the therapeutic course, but rather involves a broad pattern of different resistance classes, including multidrug resistance, as well as resistance to macrolides, aminoglycosides, tetracyclines and beta-lactams. Our data stress the relevance of mapping the gut resistome in HSCT pediatric patients to define the most appropriate anti-infective treatment post HSCT.

International audience; The global increases in life expectancy and population have resulted in a growing ageing population and with it a growing number of people living with age-related neurodegenerative conditions and dementia, shifting focus towards methods of prevention, with lifestyle approaches such as nutrition representing a promising avenue for further development.This overview summarises the main themes discussed during the 3rd Symposium on “Nutrition for the Ageing Brain: Moving Towards Clinical Applications” held in Madrid in August 2018, enlarged with the current state of knowledge on how nutrition influences healthy ageing and gives recommendations regarding how the critical field of nutrition and neurodegeneration research should move forward into the future.Specific nutrients are discussed as well as the impact of multi-nutrient and whole diet approaches, showing particular promise to combatting the growing burden of age-related cognitive decline. The emergence of new avenues for exploring the role of diet in healthy ageing, such as the impact of the gut microbiome and development of new techniques (imaging measures of brain metabolism, metabolomics, biomarkers) are enabling researchers to approach finding answers to these questions. But the translation of these findings into clinical and public health contexts remains an obstacle due to significant shortcomings in nutrition research or pressure on the scientific community to communicate recommendations to the general public in a convincing and accessible way. Some promising programs exist but further investigation to improve our understanding of the mechanisms by which nutrition can improve brain health across the human lifespan is still required.

The gut microbiota appears to be a significant contributor to musculoskeletal health and disease. Genetic background, age, gender, diet, lifestyle and socio-economic aspects are also important factors that contribute to musculoskeletal health, as well as to the normal balance of the intestinal microbiota. Through the production of a large and diverse pool of bioactive small molecules, the gut microbiota can in fact signal to extra-intestinal organs, establishing a systems-level connection with the host metabolic, endocrine, immune and nervous apparatus. The gut microbiota has therefore been extensively studied in recent years, for health promotion, disease prevention and disease treatment, as well as for exercise performance. Practically, physical activity is recommended as a useful tool to prevent disease and improve prognosis when an athlete gets sick or injured. Therefore, the findings of studies performed on athletes should not be automatically transferred to all subjects undertaking non-competitive exercise.

Diet can affect the diversity and composition of gut microbiota. Usage of antibiotics in food production and in human or veterinary medicine has resulted in the emergence of commensal antibiotic resistant bacteria in the human gut. The incidence of erythromycin-resistant lactic acid bacteria (LAB) in the feces of healthy vegans, ovo-lacto vegetarians and omnivores was analyzed. Overall, 155 LAB were isolated and characterized for their phenotypic and genotypic resistance to erythromycin. The isolates belonged to 11 different species within the Enterococcus and Streptococcus genera. Enterococcus faecium was the dominant species in isolates from all the dietary categories. Only 97 out of 155 isolates were resistant to erythromycin after Minimum Inhibitory Concentration (MIC) determination; among them, 19 isolates (7 from vegans, 4 from ovo-lacto vegetarians and 8 from omnivores) carried the erm(B) gene. The copresence of erm(B) and erm(A) genes was only observed in Enterococcus avium from omnivores. Moreover, the transferability of erythromycin resistance genes using multidrug-resistant (MDR) cultures selected from the three groups was assessed, and four out of six isolates were able to transfer the erm(B) gene. Overall, isolates obtained from the omnivore samples showed resistance to a greater number of antibiotics and carried more tested antibiotic resistance genes compared to the isolates from ovo-lacto vegetarians and vegans. In conclusion, our results show that diet does not significantly affect the occurrence of erythromycin-resistant bacteria and that commensal strains may act as a reservoir of antibiotic resistance (AR) genes and as a source of antibiotic resistance spreading.

The modern Paleolithic diet (MPD), featured by the consumption of vegetables, fruit, nuts, seeds, eggs, fish and lean meat, while excluding grains, dairy products, salt and refined sugar, has gained substantial public attention in recent years because of its potential multiple health benefits. However, to date little is known about the actual impact of this dietary pattern on the gut microbiome (GM) and its implications for human health. In the current scenario where Western diets, low in fiber while rich in industrialized and processed foods, are considered one of the leading causes of maladaptive GM changes along human evolution, likely contributing to the increasing incidence of chronic non-communicable diseases, we hypothesize that the MPD could modulate the Western GM towards a more “ancestral” configuration. In an attempt to shed light on this, here we profiled the GM structure of urban Italian subjects adhering to the MPD, and compared data with other urban Italians following a Mediterranean Diet (MD), as well as worldwide traditional hunter-gatherer populations from previous publications. Notwithstanding a strong geography effect on the GM structure, our results show an unexpectedly high degree of biodiversity in MPD subjects, which well approximates that of traditional populations. The GM of MPD individuals also shows some peculiarities, including a high relative abundance of bile-tolerant and fat-loving microorganisms. The consumption of plant-based foods–albeit with the exclusion of grains and pulses–along with the minimization of the intake of processed foods, both hallmarks of the MPD, could therefore contribute to partially rewild the GM but caution should be taken in adhering to this dietary pattern in the long term.

Background Even if horses strictly depend on the gut microbiota for energy homeostasis, only a few molecular studies have focused on its characterisation and none on the perinatal gut microbial colonisation process. Objectives To explore the perinatal colonisation process of the foal gut microbial ecosystem and the temporal dynamics of the ecosystem assembly during the first days of life. Study design Longitudinal study. Methods Thirteen Standardbred mare-foal pairs were included in the study. For each pair, at delivery we collected the mare amniotic fluid, faeces and colostrum, and the foal meconium. Milk samples and faeces of both mare and foal were also taken longitudinally, until day 10 post-partum. Samples were analysed by means of next-generation sequencing of the 16S rRNA gene on Illumina MiSeq. Results Our findings suggest that microbial components derived from the mare symbiont communities establishes in the foal gut since fetal life. After birth, an external transmission route of mare microorganisms takes place. This involves a rapid and dynamic process of assembling the mature foal gut microbiome, in which the founder microbial species are derived from both the milk and the gut microbial ecosystems of the mare. Main limitations The inability to discriminate between live and dead cells, the possible presence of contaminating bacteria in low biomass samples (e.g. meconium and amniotic fluid), the limits of the phylogenetic assignment down to species level, and the presence of unassigned operational taxonomic units. Conclusions Our data highlight the importance of mare microbiomes as a key factor for the establishment of the gut microbial ecosystem of the foal.

Mother's own milk represents the optimal source for preterm infant nutrition, as it promotes immune defenses and gastrointestinal function, protects against necrotizing enterocolitis, improves long-term clinical outcome and is hypothesized to drive gut microbiota assembly. Preterm infants at birth usually do not receive their mother's milk directly from the breast, because active suckling and coordination between suckling, swallowing and breathing do not develop until 32-34 weeks gestational age, but actual breastfeeding is usually possible as they grow older. Here, we enrolled moderately preterm infants (gestational age 32-34 weeks) to longitudinally characterize mothers' milk and infants' gut and oral microbiomes, up to more than 200 days after birth, through 16S rRNA sequencing. This peculiar population offers the chance to disentangle the differential contribution of human milk feeding per se vs. actual breastfeeding in the development of infant microbiomes, that have both been acknowledged as crucial contributors to short and long-term infant health status. In this cohort, the milk microbiome composition seemed to change following the infant's latching to the mother's breast, shifting toward a more diverse microbial community dominated by typical oral microbes, i.e., Streptococcus and Rothia. Even if all infants in the present study were fed human milk, features typical of healthy, full term, exclusively breastfed infants, i.e., high percentages of Bifidobacterium and low abundances of Pseudomonas in fecal and oral samples, respectively, were detected in samples taken after actual breastfeeding started. These findings underline the importance of encouraging not only human milk feeding, but also an early start of actual breastfeeding in preterm infants, since the infant's latching to the mother's breast might constitute an independent factor helping the health-promoting assembly of the infant gut microbiome.

Background (Trans)-3,7-Dimethyl-2,6-octadien-1-ol, commonly called geraniol (Ge-OH), is an acyclic monoterpene alcohol with well-known anti-inflammatory and antimicrobial properties. Ge-OH is a non-toxic compound classified as Generally Recognized As Safe (GRAS) by the US Food and Drug Administration and the European Food Security Agency. Methods Ge-OH was orally administered at a maximum daily dose of 8 mg kg(− 1) body weight for four weeks in a delayed release formulation capable of reaching the colon. Fecal microbiota and blood cytokines were analyzed before and after Ge-OH treatment, as well as IBS symptomatology by using Visual Analogue Scale (VAS-IBS). Results The results show that orally administered Ge-OH is a powerful modulator of the intestinal microbial ecosystem, capable of leading to increased relative abundances of Collinsella and especially Faecalibacterium, a well-known health-promoting butyrate producer consistently found to be decreased in IBS patients. Moreover, Ge-OH strongly improved the clinical symptoms of colitis by significantly reducing the score recorded by the VAS-IBS questionnaire. Clinical improvement was associated with a significant reduction in the circulating MIP-1β, a chemokine found to be increased in several IBS patients. Conclusion Ge-OH could be a powerful component for food supplement targeted to the treatment of IBS patients. Trial registration ISRCTN47041881, retrospectively registered on 19th July 2018.

Gut microbiota, the specific microbial community of the gastrointestinal tract, by means of the production of microbial metabolites provides the host with several functions affecting metabolic and immunological homeostasis. Insights into the intricate relationships between gut microbiota and the host require not only the understanding of its structure and function but also the measurement of effector molecules acting along the gut microbiota axis. This article reviews the literature on targeted chromatographic approaches in analysis of gut microbiota specific metabolites in feces as the most accessible biological matrix which can directly probe the connection between intestinal bacteria and the (patho)physiology of the holobiont. Together with a discussion on sample collection and preparation, the chromatographic methods targeted to determination of some classes of microbiota-derived metabolites (e.g., short-chain fatty acids, bile acids, low molecular masses amines and polyamines, vitamins, neurotransmitters and related compounds) are discussed and their main characteristics, summarized in Tables.

The High Taxonomic Fingerprint (HTF)-Microbi.Array is a fully validated phylogenetic microarray platform for a high taxonomic level characterization of the human gut microbiota. However, suffering from PCR-dependent biases in Bifidobacterium quantification, this tool is less appropriate when utilized for the characterization of the Bifidobacterium -dominated gut microbiota of breast-fed infants. To overcome this, we implemented a new combined approach based on HTF-Microbi.Array and qPCR for a reliable fingerprint of the infant-type microbiota. This methodology was applied in a preliminary comparative study of the faecal microbiota of eight breast-fed infants, aged 2–6 months, and five young adults. Whereas the adult gut microbiota was largely dominated by Firmicutes and Bacteroidetes , the infant-type community was mainly dominated by Bifidobacterium , with Enterobacteriaceae as the second dominant component. In accordance with the most recent literature in the field, the obtained microbiota fingerprints properly depicted the adult- and the infant-type microbiota, demonstrating the reliability of the HTF-Microbi.Array/qPCR combined approach in reflecting the peculiarities of the two intestinal microbial ecosystems.

Therapeutic hypothermia is today used in several clinical settings, among them the gut related diseases that are influenced by ischemia/reperfusion injury. This perspective paved the way to the study of hibernation physiology, in natural hibernators, highlighting an unexpected importance of the gut microbial ecosystem in hibernation and torpor. In natural hibernators, intestinal microbes adaptively reorganize their structural configuration during torpor, and maintain a mutualistic configuration regardless of long periods of fasting and cold temperatures. This allows the gut microbiome to provide the host with metabolites, which are essential to keep the host immunological and metabolic homeostasis during hibernation. The emerging role of the gut microbiota in the hibernation process suggests the importance of maintaining a mutualistic gut microbiota configuration in the application of therapeutic hypothermia as well as in the development of new strategy such as the use of synthetic torpor in humans. The possible utilization of tailored probiotics to mold the gut ecosystem during therapeutic hypothermia can also be taken into consideration as new therapeutic strategy.

The ageing process affects the human gut microbiota phylogenetic composition and its interaction with the immune system. Age-related gut microbiota modifications are associated with immunosenescence and inflamm-ageing in a sort of self-sustaining loop, which allows the placement of gut microbiota unbalances among both the causes and the effects of the inflamm-ageing process. Even if, up to now, the link between gut microbiota and the ageing process is only partially understood, the gut ecosystem shows the potential to become a promising target for strategies able to contribute to the health status of older people. In this context, the consumption of pro/prebiotics may be useful in both prevention and treatment of age-related pathophysiological conditions, such as recovery and promotion of immune functions, i.e. adjuvant effect for influenza vaccine, and prevention and/or alleviation of common “winter diseases”, as well as constipation and Clostridium difficile -associated diarrhoea. Moreover, being involved in different mechanisms which concur in counteracting inflammation, such as down-regulation of inflammation-associated genes and improvement of colonic mucosa conditions, probiotics have the potentiality to be involved in the promotion of longevity.

Human plasmin(ogen) is regarded as a component of the molecular cross talk between the probiotic species Bifidobacterium animalis subsp. lactis and the human host. However, up to now, only in vitro studies have been reported. Here, we demonstrate that the probiotic strain B. animalis subsp. lactis BI07 is capable of recruiting plasmin(ogen) present at physiological concentrations in crude extracts from human feces. Our results provide evidence that supports the significance of the B. lactis -plasmin(ogen) interaction in the human gastrointestinal tract.

The interaction with the host plasminogen/plasmin system represents a novel component in the molecular cross-talk between bifidobacteria and human host. Here, we demonstrated that the plasminogen-binding bifidobacterial species B. longum, B. bifidum, B. breve and B. lactis share the key glycolytic enzyme enolase as a surface receptor for human plasminogen. Enolase was visualized on the cell surface of the model strain B. lactis BI07. The His-tagged recombinant protein showed a high affinity for human plasminogen, with an equilibrium dissociation constant in the nanomolar range. By site-directed mutagenesis we demonstrated that the interaction between the B. lactis BI07 enolase and human plasminogen involves an internal plasminogen-binding site homologous to that of pneumococcal enolase. According to our data, the positively charged residues Lys-251 and Lys-255, as well as the negatively charged Glu-252, of the B. lactis BI07 enolase are crucial for plasminogen binding. Acting as a human plasminogen receptor, the bifidobacterial surface enolase is suggested to play an important role in the interaction process with the host.

Bifidobacteria constitute up to 3% of the total microbiota and represent one of the most important health-promoting bacterial groups of the human intestinal microflora. The presence ofBifidobacteriumin the human gastrointestinal tract has been directly related to several health-promoting activities; however, to date, no information about the specific mechanisms of interaction with the host is available. In order to provide some insight into the molecular mechanisms involved in the interaction with the host, we investigated whetherBifidobacteriumwas able to capture human plasminogen on the cell surface. By using flow cytometry, we demonstrated a dose-dependent human plasminogen-binding activity for four strains belonging to three bifidobacterial species:Bifidobacterium lactis,B. bifidum, andB. longum. The binding of human plasminogen toBifidobacteriumwas dependent on lysine residues of surface protein receptors. By using a proteomic approach, we identified five putative plasminogen-binding proteins in the cell wall fraction of the model strainB. lactisBI07. The data suggest that plasminogen binding toB. lactisis due to the concerted action of a number of proteins located on the bacterial cell surface, some of which are highly conserved cytoplasmic proteins which have other essential cellular functions. Our findings represent a step forward in understanding the mechanisms involved in theBifidobacterium-host interaction.